Mitophagy is an autophagic process that degrades mitochondria by an intracellular engulfment that leads to their delivery into the lumen of the cell's hydrolytic compartment, such as the lysosome in animal cells or the vacuole in yeast. It is hypothesized that such processes serve a quality control function to prevent or slow the accumulation of malfunctioning mitochondria, which are thought in turn to underlie central aspects of the aging process in eukaryotic organisms. We recently identified a conserved mitochondrial protein phosphatase homolog, Aup1, which is required for efficient stationary phase mitophagy in yeast. In the present report, we demonstrate that the retrograde signaling pathway (RTG) is defective in aup1⌬ mutants. In agreement with a role for Aup1 in the regulation of the RTG pathway, we find that deletion of RTG3, a transcription factor that mediates the RTG response, causes a defect in stationary phase mitophagy and that deletion of AUP1 leads to changes in Rtg3 phosphorylation patterns under these conditions. In addition, we find that mitophagic conditions lead to induction of RTG pathway target genes in an Aup1-dependent fashion. Thus, our results suggest that the function of Aup1 in mitophagy could be explained through its regulation of Rtg3-dependent transcription.Mitochondria play an essential role in the physiology of eukaryotic cells. They are the sites of aerobic energy production and biosynthesis of amino acid precursors as well as nucleotide and lipid production. At the same time, mitochondria also present a threat to the cell, through production of reactive oxygen species and through the potential leakage of toxic factors, such as cytochrome c.It is generally hypothesized that quality control mechanisms scavenge malfunctioning mitochondrial compartments, safely neutralizing them before they damage cellular physiology (1, 2). One such quality control mechanism is autophagy, a catabolic process used by cells to transport cytoplasmic material for degradation in the lysosome (in animal cells) or the vacuole (in yeast, filamentous fungi, and plants) (3)(4)(5). Autophagic pathways can be classified either according to their molecular mechanism or according to their specificity. Thus, macroautophagy, the most well studied form of autophagy, is thought to be a relatively nonspecific scavenging mechanism that is induced in response to starvation cues (6 -8). Mechanistically, macroautophagy involves the generation of a cytosolic intermediate, an autophagosome, that consequently fuses with the lytic compartment or with elements of the endomembrane system that flow into the lytic compartment. On the other hand, microautophagy is a form of autophagy that involves direct involution of the vacuolar membrane, thus allowing import of material into the vacuolar lumen for degradation. There are several well documented types of selective autophagy. When Pichia pastoris is grown on methanol as a carbon source, it massively induces peroxisomes. When these cells are shifted to a better carbon source, su...
